Roles of very long-chain fatty acids in compound leaf patterning in Medicago truncatula.

Plant cuticles are composed of hydrophobic cuticular waxes and cutin. Very long-chain fatty acids (VLCFAs) are components of epidermal waxes and the plasma membrane and are involved in organ morphogenesis. By screening a barrelclover (Medicago truncatula) mutant population tagged by the transposable element of tobacco (Nicotiana tabacum) cell type1 (Tnt1), we identified two types of mutants with unopened flower phenotypes, named unopened flower1 (uof1) and uof2. Both UOF1 and UOF2 encode enzymes that are involved in the biosynthesis of VLCFAs and cuticular wax. Comparative analysis of the mutants indicated that the mutation in UOF1, but not UOF2, leads to the increased number of leaflets in M. truncatula. UOF1 was specifically expressed in the outermost cell layer (L1) of the shoot apical meristem (SAM) and leaf primordia. The uof1 mutants displayed defects in VLCFA-mediated plasma membrane integrity, resulting in the disordered localization of the PIN-FORMED1 (PIN1) ortholog SMOOTH LEAF MARGIN1 (SLM1) in M. truncatula. Our work demonstrates that the UOF1-mediated biosynthesis of VLCFAs in L1 is critical for compound leaf patterning, which is associated with the polarization of the auxin efflux carrier in M. truncatula.

Application and advances of biomimetic membrane materials in central nervous system disorders.

Central nervous system (CNS) diseases encompass spinal cord injuries, brain tumors, neurodegenerative diseases, and ischemic strokes. Recently, there has been a growing global recognition of CNS disorders as a leading cause of disability and death in humans and the second most common cause of death worldwide. The global burdens and treatment challenges posed by CNS disorders are particularly significant in the context of a rapidly expanding global population and aging demographics. The blood-brain barrier (BBB) presents a challenge for effective drug delivery in CNS disorders, as conventional drugs often have limited penetration into the brain. Advances in biomimetic membrane nanomaterials technology have shown promise in enhancing drug delivery for various CNS disorders, leveraging properties such as natural biological surfaces, high biocompatibility and biosafety. This review discusses recent developments in biomimetic membrane materials, summarizes the types and preparation methods of these materials, analyzes their applications in treating CNS injuries, and provides insights into the future prospects and limitations of biomimetic membrane materials.

A novel explainable online calculator for contrast-induced AKI in diabetics: a multi-centre validation and prospective evaluation study.

BACKGROUND: In patients undergoing percutaneous coronary intervention (PCI), contrast-induced acute kidney injury (CIAKI) is a frequent complication, especially in diabetics, and is connected with severe mortality and morbidity in the short and long term. Therefore, we aimed to develop a CIAKI predictive model for diabetic patients. METHODS: 3514 patients with diabetes from four hospitals were separated into three cohorts: training, internal validation, and external validation. We developed six machine learning (ML) algorithms models: random forest (RF), gradient-boosted decision trees (GBDT), logistic regression (LR), least absolute shrinkage and selection operator with LR, extreme gradient boosting trees (XGBT), and support vector machine (SVM). The area under the receiver operating characteristic curve (AUC) of ML models was compared to the prior score model, and developed a brief CIAKI prediction model for diabetes (BCPMD). We also validated BCPMD model on the prospective cohort of 172 patients from one of the hospitals. To explain the prediction model, the shapley additive explanations (SHAP) approach was used. RESULTS: In the six ML models, XGBT performed best in the cohort of internal (AUC: 0.816 (95% CI 0.777-0.853)) and external validation (AUC: 0.816 (95% CI 0.770-0.861)), and we determined the top 15 important predictors in XGBT model as BCPMD model variables. The features of BCPMD included acute coronary syndromes (ACS), urine protein level, diuretics, left ventricular ejection fraction (LVEF) (%), hemoglobin (g/L), congestive heart failure (CHF), stable Angina, uric acid (umol/L), preoperative diastolic blood pressure (DBP) (mmHg), contrast volumes (mL), albumin (g/L), baseline creatinine (umol/L), vessels of coronary artery disease, glucose (mmol/L) and diabetes history (yrs). Then, we validated BCPMD in the cohort of internal validation (AUC: 0.819 (95% CI 0.783-0.855)), the cohort of external validation (AUC: 0.805 (95% CI 0.755-0.850)) and the cohort of prospective validation (AUC: 0.801 (95% CI 0.688-0.887)). SHAP was constructed to provide personalized interpretation for each patient. Our model also has been developed into an online web risk calculator. MissForest was used to handle the missing values of the calculator. CONCLUSION: We developed a novel risk calculator for CIAKI in diabetes based on the ML model, which can help clinicians achieve real-time prediction and explainable clinical decisions.

Optimization of Catalysts and Conditions in Gold(I) Catalysis-Counterion and Additive Effects.

Gold catalysis has proven to be an important breakthrough for organic synthesis. The tunable nature of gold catalysts, the unique properties of gold, and the mild reaction conditions required in many gold-catalyzed reactions have all contributed substantially to this metal's popularity in catalysis. However, gold-catalyzed reactions still suffer from limitations such as low turnover numbers (TON). Optimization of the catalysts and reaction conditions may significantly improve the efficiency of gold-catalyzed reactions. In this review, we will present leading examples of counterion or additive-regulated gold catalysis from a mechanistic perspective. We will pay special attention to the physical properties of counterion/additive, such as gold affinity and hydrogen bond basicity, and discuss their effects on the reactivity of gold catalysts.

Late Elongated Hypocotyl Positively Regulates Salt Stress Tolerance in Medicago truncatula.

Abiotic stress, such as drought, osmotic, and salinity stresses, seriously affects plant growth and crop production. Studying stress-resistant genes that enhance plant stress tolerance is an efficient way to facilitate the breeding of crop species with high stress tolerance. In this study, we reported that the core circadian clock component, the LATE ELONGATED HYPOCOTYL (LHY) orthologue MtLHY, plays a positive role in salt stress response in Medicago truncatula. The expression of MtLHY was induced by salt stress, and loss-of-function mutants of MtLHY were shown to be hypersensitive to salt treatment. However, overexpression of MtLHY improved salt stress tolerance through a higher accumulation of flavonoids. Consistently, exogenous flavonol application improved the salt stress tolerance in M. truncatula. Additionally, MtLHY was identified as a transcriptional activator of the flavonol synthase gene, MtFLS. Our findings revealed that MtLHY confers plant salt stress tolerance, at least by modulating the flavonoid biosynthesis pathway, which provides insight into salt stress tolerance that links the circadian clock with flavonoid biosynthesis.

Comparison of C-Arm-Free Oblique Lumbar Interbody Fusion L5-S1 (OLIF51) with Transforaminal Lumbar Interbody Fusion L5-S1 (TLIF51) for Adult Spinal Deformity.

Background and Objectives: Adult spinal deformity (ASD) surgery, L5-S1 lordosis is very important factor. The main objective of the research is to retrospectively compare symptomatic presentation and radiological presentation in the sequelae of oblique lumbar inter-body spinal fusion at L5-S1 (OLIF51) and transforaminal lumbar interbody fusion (TLIF) for ASD. Materials and Methods: We retrospectively evaluated 54 patients who underwent corrective spinal fusion for ASD between October 2019 and January 2021. Thirteen patients underwent OLIF51 (average 74.6 years old, group O) and 41 patients underwent TLIF51 (average 70.5 years old, group T). Mean follow-up period was 23.9 months for group O and 28.9 months for group T, ranging from 12 to 43 months. Clinical and radiographic outcomes are assessed using values including visual analogue scale (VAS) for back pain and Oswestry disability index (ODI). Radiographic evaluation was also collected preoperatively and at 6, 12, and 24 months postoperatively. Results: Surgical time in group O was less than that in group T (356 min vs. 492 min, p = 0.003). However, intraoperative blood loss of both groups were not significantly different (1016 mL vs. 1252 mL, p = 0.274). Changes in VAS and ODI were similar in both groups. L5-S1 angle gain and L5-S1 height gain in group O were significantly better than those of group T (9.4° vs. 1.6°, p = 0.0001, 4.2 mm vs. 0.8 mm, p = 0.0002). Conclusions: Clinical outcomes were not significantly different in both groups, but surgical time in OLIF51 was significantly less than that in TLIF51. The radiographic outcomes showed that OLIF51 created more L5-S1 lordosis and L5-S1 disc height compared with TLIF 51.

Gold (I/III)-Catalyzed Trifluoromethylthiolation and Trifluoromethylselenolation of Organohalides.

The first C-SCF3 /SeCF3 cross-coupling reactions using gold redox catalysis [(MeDalphos)AuCl], AgSCF3 or Me4 NSeCF3 , and organohalides as substrates are reported. The new methodology enables a one-stop shop synthesis of aryl/alkenyl/alkynyl trifluoromethylthio- and selenoethers with a broad substrate scope (>60 examples with up to 97 % isolated yield). The method is scalable, and its robustness is evidenced by the late-stage functionalization of various bioactive molecules, which makes this reaction an attractive alternative in the synthesis of trifluoromethylthio- and selenoethers for pharmaceutical and agrochemical research and development.

Interaction between the MtDELLA-MtGAF1 Complex and MtARF3 Mediates Transcriptional Control of MtGA3ox1 to Elaborate Leaf Margin Formation in Medicago truncatula.

The molecular mechanisms underlying the diversity of leaf shapes have been of great interest to researchers. Leaf shape depends on the pattern of serrations and the degree of indentation of leaf margins. Multiple transcription factors and hormone signaling pathways are involved in this process. In this study, we characterized the developmental roles of SMALL AND SERRATED LEAF (SSL) by analyzing a recessive mutant in the model legume Medicago truncatula. An ortholog of Arabidopsis thaliana GA3-oxidase 1 (GA3ox1), MtGA3ox1/SSL, is required for GA biosynthesis. Loss of function in MtGA3ox1 results in the small plant and lateral organs. The prominent phenotype of the mtga3ox1 mutant is a more pronounced leaf margin, indicating the critical role of GA level in leaf margin formation. Moreover, 35S:MtDELLA2ΔDELLA and 35S:MtARF3 transgenic plants display leaves with a deeply wavy margin, which resembles those of mtga3ox1. Further investigations show that MtGA3ox1 is under the control of MtDELLA1/2/3-MtGAF1 complex-dependent feedback regulation. Further, MtARF3 behaves as a competitive inhibitor of MtDELLA2/3-MtGAF1 complexes to repress the expression of MtGA3ox1 indirectly. These findings suggest that GA feedback regulatory circuits play a fundamental role in leaf margin formation, in which the posttranslational interaction between transcription factors functions as an additional feature.

Trifluoromethyl Nonaflate: A Practical Trifluoromethoxylating Reagent and its Application to the Regio- and Stereoselective Synthesis of Trifluoromethoxylated Alkenes.

The trifluoromethoxy group has elicited much interest among drug and agrochemical discovery teams because of its unique properties. We developed trifluoromethyl nonafluorobutanesulfonate (nonaflate), TFNf, an easy-to-handle, bench-stable, reactive, and scalable trifluoromethoxylating reagent. TFNf is easily and safely prepared in a simple process in large scale and the nonaflyl part of TFNf can easily be recovered as nonaflyl fluoride after usage and recycled. The synthetic potency of TFNf was showcased with the underexplored synthesis of various trifluoromethoxylated alkenes, through a high regio- and stereoselective hydro(halo)trifluoromethoxylation of alkyne derivatives such as haloalkynes, alkynyl esters, and alkynyl sulfones. The synthetic merits of TFNf were further underscored with a high-yielding and smooth nucleophilic trifluoromethoxylation of alkyl triflates/bromides and primary/secondary alcohols.

Improving Homogeneous Cationic Gold Catalysis through a Mechanism-Based Approach.

Homogeneous gold catalysis is regarded as a landmark addition to the field of organic synthesis. It is the most effective way to activate alkynes for the addition of a diverse host of nucleophiles. However, the literature reveals that a relatively high catalyst loading is needed in many gold-catalyzed applications (1-10 mol %), which is impractical in large-scale synthesis or multistep synthesis because of the high price and recyclization difficulty of the gold. A more thorough understanding of the factors that operate on homogeneous gold catalysis can provide better guidelines for the future design of more efficient gold-catalyzed reactions. In this Account, we will summarize our group's extensive investigation of factors impacting cationic gold catalysis, namely, the effects of ligands, counterions, additives, and catalyst decay and deactivation, using a mechanism-based approach with the aim of improving the efficiency of homogeneous gold catalysis. Through NMR-assisted kinetic studies, we investigated the above factors. Our systematic ligand effect investigation provided a clearer understanding of how ligands influence each of the three stages in the gold catalytic cycle. On the basis of this study, we synthesized a novel phosphine ligand and achieved parts per million-level gold catalysis by manipulating the electron density of the substituents and the steric strain around phosphorus. Our investigation of counterion effects led to the design of a gold affinity index and hydrogen-bonding basicity index for counterions, which can forecast the reactivity of counterions in cationic gold catalysis. We studied the adverse silver effects in cationic gold catalyst activation and proposed a more efficient practical guide. Our additive effect investigation revealed that additives that are good hydrogen-bond acceptors increase the efficiency of gold-catalyzed reactions in those occurrences where protodeauration is the rate-determining step. The first detailed experimental analysis of gold catalyst decay and the influence of each component in the reaction system (substrate, counterion, solvent) on the decay process was also conducted. We found that high-gold-affinity impurities (halides, bases) in solvents, starting materials, filtration, or drying agents decrease the reactivity of a gold catalyst but that a suitable acid activator can reactivate the gold catalyst and enable the reaction to proceed smoothly at competitively low gold catalyst loadings. The effects of acid additives were also systematically investigated using typical reactions. We are convinced that better mechanistic understandings will offer clearer guidelines for the search for more efficient gold-catalyzed reactions.

Revisiting the role of acids and hydrogen bond acceptors in enamine formation.

A systematic investigation into the effects of acids and hydrogen bond acceptors on the reaction rates and equilibria of enamine formation is reported. Acids can accelerate the reaction but do not change the reaction equilibria. In comparison, hydrogen bond acceptors facilitate the enamine formation via their strong hydrogen bonding interaction with the water generated in the reaction.

Genome-wide characterization of SPL family in Medicago truncatula reveals the novel roles of miR156/SPL module in spiky pod development.

BACKGROUND: SQUAMOSA Promoter Binding Protein-Likes (SPLs) proteins are plant-specific transcription factors that play many crucial roles in plant growth and development. However, there is little information about SPL family in the model legume Medicago truncatula. RESULTS: In this study, a total of 23 MtSPL genes were identified in M. truncatula genome, in which 17 of the MtSPLs contained the putative MtmiR156 binding site at the coding or 3' UTR regions. Tissue-specific expression pattern analysis showed that most MtmiR156-targeted MtSPLs were highly expressed in seed and pod. The observation of MtmiR156B-overexpressing plants reveals that MtmiR156/MtSPL modules are not only involved in the development of leaves and branches, but also in the seed pod development, especially the formation of spine on pod. CONCLUSION: The spines on pods are developed in many plant species, which allow pods to adhere to the animals, and then be transported on the outside. This study sheds light on the new function of SPL family in seed dispersal by controlling the formation of spiky pod, and provides insights on understanding evolutionary divergence of the members of SPL gene family among plant species.

Recyclable cellulose-palladium nanoparticles for clean cross-coupling chemistry.

Cheap, recyclable, and robust cellulose-palladium nanoparticles were developed and fully characterized by FTIR, TEM, XPS, TGA, and NMR. The nanoparticles enabled cross-coupling chemistry in a truly general fashion i.e., Suzuki-Miyaura, Heck, Sonogashira, and C-H activation. Notably, all types of transformations were achieved with a single type of nanocatalyst. Complete recyclability of the catalyst and low traces of palladium in the product demonstrates the greenness of the protocol.

Comparative Evaluation of Soluble and Insoluble-Bound Phenolics and Antioxidant Activity of Two Chinese Mistletoes.

Mistletoes are used medicinally in order to treat various human illnesses. Few studies have reported on the phenolic content and antioxidant properties of Chinese mistletoes (CMs). In this work, the total phenolic content (TPC), total flavonoid content (TFC), and antioxidant activities of soluble and insoluble-bound phenolic extracts from CMs hosted by Camellia assamica (Mast.) Chang (CMC) and Pyrus, i, f. (CMP) were compared. Phenolic compounds in CMC and CMP were identified and quantified using high-performance liquid chromatography (HPLC). The results indicated that the TPC of soluble phenolic extracts was higher than insoluble-bound phenolic counterparts in both CMC and CMP. In addition, the TPC of soluble, insoluble-bound and total phenolic fractions (9.91 ± 0.23, 4.59 ± 0.27 and 14.50 ± 0.35 µmol ferulic acid equivalents per gram (FAE/g) dry sample) extracted from CMP were higher than those extracted from CMC. The soluble phenolic extracts in CMP showed higher antioxidant activities than those in CMC. Eighteen phenolic compounds from soluble and insoluble-bound phenolic extracts from the CMs were identified and quantified by HPLC. This study indicates that CMC and CMP, especially the latter, could be sources of antioxidants in human health care.

Widely Applicable Hydrofluorination of Alkenes via Bifunctional Activation of Hydrogen Fluoride.

Expanding the use of fluorine in pharmaceuticals, agrochemicals and materials requires a widely applicable and more efficient protocol for the preparation of fluorinated compounds. We have developed a new generation nucleophilic fluorination reagent, KHSO4-13HF, HF 68 wt/wt %, that is not only easily handled and inexpensive but also capable of hydrofluorinating diverse, highly functionalized alkenes, including natural products. The high efficiency observed in this reaction hinges on the activation of HF using a highly "acidic" hydrogen bond acceptor.

MicroRNA 200a inhibits erythroid differentiation by targeting PDCD4 and THRB.

Previous studies on erythropoiesis revealed that microRNAs (miRNAs) play a critical role in erythroid differentiation. Given the abundance of identified miRNAs and the limited understanding of erythroid miRNAs, additional examination is required. Here, two sets of erythroid differentiation miRNome data were analysed to screen for novel erythroid-inhibiting miRNAs. MIR200A was selected based on its pattern of downregulated expression in the miRNome datasets during induction of erythroid differentiation. Overexpression of MIR200A in K562 and TF-1 cells confirmed its inhibitory role in erythroid differentiation. Further in vivo study indicated that overexpression of mir200a inhibited primitive erythropoiesis of zebrafish. Transcriptome analyses after MIR200A overexpression in TF-1 cells indicated a significant role in regulating erythroid function and revealed potential regulation networks. Additionally, bioinformatics and experimental analyses confirmed that PDCD4 (programmed cell death 4) and THRB (thyroid hormone receptor, beta) are both targets of MIR200A-3p. Gain- and loss-of-function studies of PDCD4 and THRB revealed that the two targets were capable of promoting erythroid gene expression. Overall, our results revealed that microRNA 200a inhibits erythroid differentiation by targeting PDCD4 and THRB.

Gold-catalyzed Fluorination of Alkynyl Esters and Ketones: Efficient Access to Fluorinated 1,3-Dicarbonyl Compounds.

We developed an efficient synthesis of 2-fluoro-1,3-dicarbonyl compounds using readily available alkynyl ketones or esters as starting material. The key step is the insertion of hydrogen fluoride (HF) to the gold carbene intermediate generated from cationic gold catalyzed addition of N-oxides to alkynyl ketones or esters. This method gives excellent chemical yields and regioselectivity with good functional group tolerance.

Metal-free, Regio-, and Stereo-Controlled Hydrochlorination and Hydrobromination of Ynones and Ynamides.

We developed an atom-economical and metal-free method for the regio- and stereo-selective hydrohalogenation of ynones and ynamides using easy to handle DMPU/HX (X = Br or Cl) reagents. The reaction operates under mild conditions and a range of functional groups is well tolerated. We propose that the hydrohalogenation of ynones gives the anti-addition products via a concerted multimolecular AdE3 mechanism and that the hydrohalogenation of ynamides produces the syn-addition products via a cationic keteniminium intermediate.

The distribution of vascular endothelial growth factor in human meniscus and a meniscal injury model.

BACKGROUND: The meniscus plays an important role in controlling the complex biomechanics of the knee. Meniscus injury is common in the knee joint. The perimeniscal capillary plexus supplies the outer meniscus, whereas the inner meniscus is composed of avascular tissue. Angiogenesis factors, such as vascular endothelial growth factor (VEGF), have important roles in promoting vascularization of various tissues. VEGF-mediated neovascularization is beneficial to the healing of injured tissues. However, the distribution and angiogenic role of VEGF remains unclear in the meniscus and injured meniscus. We hypothesized that VEGF could affect meniscus cells and modulate the meniscus healing process. METHODS: Menisci were obtained from total knee arthroplasty patients. Meniscal injury was created ex vivo by a microsurgical blade. VEGF mRNA and protein expression were detected by the polymerase chain reaction and immunohistochemical analyses, respectively. RESULTS: In native meniscal tissue, the expression of VEGF and HIF-1α mRNAs could not be detected. However, VEGF and HIF-1α mRNAs were found in cultured meniscal cells (VEGF: outer > inner; HIF-1α: outer = inner). Injury increased mRNA levels of both VEGF and HIF-1α, with the increase being greatest in the outer area. Immunohistochemical analyses revealed that VEGF protein was detected mainly in the outer region and around injured areas of the meniscus. However, VEGF concentrations were similar between inner and outer menisci-derived media. CONCLUSIONS: This study demonstrated that both the inner and outer regions of the meniscus contained VEGF. HIF-1α expression and VEGF deposition were high in injured meniscal tissue. Our results suggest that injury stimulates the expression of HIF-1α and VEGF that may be preserved in the extracellular matrix as the healing stimulator of damaged meniscus, especially in the outer meniscus.

Acidic Co-Catalysts in Cationic Gold Catalysis.

A systematic study on the effects of Lewis or Brønsted acid co-catalysts in gold-catalyzed reactions was undertaken using representative reactions (O-, N-, and C-nucleophilic additions to alkynes). Through these reactions, it was demonstrated that an acidic co-catalyst can increase the catalyst turnover significantly, enabling practical reaction rates at competitive catalyst loadings (<1 mol %). Further investigation is currently underway to improve the understanding of the subtle principles underlying these experimental observations.